Mass spectrometry is a branch of analytical chemistry. A mass spectrometer is a device that could be said to be constructed of four basic system building blocks: (a) sample inlet system; (b) sample ionization; (c) sample ion analyzer; and (d) sample ion detection and recording. Generally, sample ionization and sample ion analyzing (b) and (c) are performed in a high vacuum, whereas, depending on methodology used, sample inlet system and ion detection and recording may or may not be included in the same high vacuum. Modern mass spectrometers tend to rely heavily upon computers to control many of their functions, as well as to collect and process the chemical data obtained.
Much basic research as well as routine quality control operations rely on mass spectrometry to provide certain data for primary identification and/or verification of the correctness of chemical structure. With a particular chemical sample in hand, the analysis commences with some form of sample introduction into the mass spectrometer. After introduction, the sample is ionized (transformed into a charged species) and transferred into some type of ion analyzer. The ion analyzer sorts and separates the ions in such a manner in order that the ion detection and recording systems of the mass spectrometer may measure the mass and intensity of each different sample ion produced from the original sample. Since most ionization techniques carry a fair amount of energy relative to the chemical sample of interest, not only an intact molecular ion species will be present, but frequently these molecular species will fragment into smaller ions. The analysis of all these ions produced from a single chemical sample can often be related back to the original un-ionized chemical sample. The mass spectrum, or collection and tabulation of all these ions produced from a single chemical sample, is highly characteristic of the original chemical sample, and is often used as a "fingerprint" for identification of the sample.
In a preliminary search of U.S. patents, the following were noted:
______________________________________ 2,767,317 - Wiley 3,939,344 - McKinney 3,480,775 - Osborne 3,949,221 - Liebl 3,590,243 - Perrin et al 3,970,854 - Boroffka et al 3,621,240 - Cohen et al 3,999,065 - Briggs 3,783,280 - Watson 4,047,030 - Lobach 3,842,266 - Thomas 4,122,343 - Risby et al 3,881,108 - Kondo et al 4,439,679 - McIlroy et al 3,931,516 - Fletcher et al 4,521,687 - Naito ______________________________________
The patents discovered by the search have revealed inventions and ideas relating to methods and devices which introduce the chemical samples, analyze the resultant sample ions, or detect the sample ions. Methods are actively being sought for maintaining high production of molecular ions while having selective control over fragmentation processes, in such a manner so as to produce fragment ions of interpretable, structural significance.
Renewed vigor in the examination of biological substances has resulted in recent innovations in analytical techniques in mass spectrometry. One area of mass spectrometry which recently has received considerable interest involves the determination of secondary ion mass spectra of chemical substances (1, 2, 2.5). The technique utilizes several means by which rapid energy deposition into a thin film of a chemical substance, which has been placed on the surface of an electrode in either the free state or as a suspension in a fluid matrix, causes sputtering (production of ions). One method of sputtering is fast atom bombardment (f.a.b.) of a sample, where the sample is introduced into the mass spectrometer and then bombarded with a beam of high energy (kilo-electron volts) neutral atoms. The fast-atom bombardment (f.a.b.) ion source will thus produce positive or negative secondary ions of the chemical substance under investigation by bombarding a suspension of the substance in a fluid matrix, deposited as a thin film on the surface of an electrode (3, 4). The method has quickly gained widespread acceptance; however, it has become evident that more extensive knowledge is necessary for a better understanding of the fundamental aspects of ion formation in order to facilitate spectral analysis.
The development and application of f.a.b. to the molecular weight determination of large, polar, thermally labile substances had been remarkably successful (1, 2). To date, most major classes of chemical compounds have been subjected to analysis by f.a.b. mass spectrometry. However, there is an ever-increasing quantity of published data which would indicate that many larger molecules of relevant biological interest do not yield ions from which significantly useful structural information can be deduced. Some instrumental parameters which affect the presence, or absence, and abundance of ions have been critically examined. Sample support surfaces (5-7), the liquid matrix (8-10), bombarding atoms (5, 6, 11), and modifications to the matrix (5-10) are some of the variables in the f.a.b. analysis which have been shown to affect the sensitivity and selectivity of f.a.b. ionization of various substances. While some aspects of the problem have been defined and delineated (12), the mechanism of ion formation under these conditions remains unresolved.